We will define and functionally characterize subpopulations of human T cells in man. This will be done by using somatic cell hybridization techniques to generate monoclonal antibodies that react specifically with thymus-dependent heteroantigens which are expressed in unique profiles by functional subsets of human T cells. We have already defined two distinct subsets of human T cells by indirect immunofluorescent binding to heterologous anti-T cell sera: 1) TH2 T cells which comprise 20-30% of peripheral T cells, and 2) TH3 T cells which comprise 60-70%. The methods applied to the detection of these subsets will also be applied to produce monoclonal antibodies directed against the relevant determinants on TH2 and TH3 cells. The ontogeny and function of TH2 T cells will then be studied using a variety of cell separation techniques, including fluorescence activated cell sorting and immunoabsorbant columns. We plan to determine the immunoregulatory activities of TH2 and TH3 T cells by studying their effects on B cell differentiation and antibody production. We will also study the alloreactivity of these subsets in terms of their proliferative and cytotoxic responses to subcomponents of the major histocompatibility complex.